It is estimated that 100 million men and women are affected by urinary incontinence (UI). The prevalence of UI is generally higher in women than in men, women being between two (older age groups) and four times (younger and middle-aged) more likely to be incontinent than men. In the past 3 years, supported by an NIH grant, we have studied the effect of pregnancy, delivery, birth trauma, ovariectomy and aging on the ultrastructure and function of the continence mechanism. We have learned that the final common pathway of stress urinary incontinence in the rat model is the alteration of nervous, vascular, and muscular components of the continence mechanism. We therefore propose to further study the molecular mechanism involved in the pathogenesis of female stress urinary incontinence. We hypothesize that pregnancy/delivery, birth trauma, and hormonal deficiency (menopause) alter the gene and protein expression of many factors. We propose to use the state-of-the-art technique such as gene microarray, realtime PCR, multiple PCR etc to identify genes that are associated with female stress urinary incontinence and to further study the molecular mechanism. Further more, we have obtained encouraging results from using organ specific acellular matrix as a scaffold for the repair of bladder and ureteral defects in our lab. We propose to study whether the acellular matrix with or without growth factors can be used for the treatment of stress urinary incontinence. The hypotheses will be tested by completing the following specific aims. Specific aim 1: To identify gene that are associated with stress incontinence and to elucidate the molecular mechanism of stress urinary incontinence associated with pregnancy/delivery, birth trauma, and ovariectomy. Specific aim 2: To identify the best growth factor combinations that can enhance angiogenesis, neural growth and urethral smooth/striated muscle proliferation in a novel in vitro assay system. Specific aim 3: To apply acellular matrix with or without growth factors identified from specific aim 2 to animals with stress urinary incontinence.